GBA moderates cognitive reserve's effect on cognitive function in patients with Parkinson's disease.

BACKGROUND: Cognitive reserve (CR) involves an individual's ability to maintain cognitive vitality over their lifespan. Glucocerebrosidase (GBA) gene mutations contribute to additional effects on cognitive function in Parkinson's disease (PD) patients, but the interplay between GBA mutations and CR remains unclear. We investigated the interactions among CR, GBA, and diseases, aiming to examine whether the CR established at different stages interacts with specific genotypes to affect cognitive function. METHODS: Three hundred and eighteen participants' CR indicators (i.e., education, occupation, and social function) and comprehensive neuropsychological function (i.e., tests for executive function, attention/working memory, visuospatial function, memory, and language) were evaluated. RESULTS: We found that CR established in a specific life stage influences the individual's cognitive function, particularly in PD, based on their distinct GBA rs9628662 genotypes. Attention/working memory and memory performance are affected by occupational complexity in midlife in PD patients with the GG genotype (q < 0.0001; q < 0.0001) and healthy adults with the T genotype (q = 0.0440; q < 0.0001). Language is influenced by early education and occupation, and the effects of occupation are also observed in PD patients with the GG genotype (q = 0.0040) and in healthy adults carrying the T genotype (q = 0.0040). CONCLUSIONS: CR, established at different life stages, can be influenced by the GBA rs9628662 genotype, impacting later-life cognition. Validating genotypes and incorporating genotype information when assessing cognitive reserve effects is crucial and can enhance targeted cognitive training.

Optoelectronic Effects of Copper-Indium-Gallium-Sulfur (CIGS2)-Solar Cells Prepared by Three-Stage Co-Evaporation Process Technology.

In this paper, the performance of Cu-(In,Ga)-S2 (CIGS2) solar cells with adjusting composite [Cu]/([Ga] + [In]) (CGI)-ratio absorber was explored and compared through an improved three-stage co-evaporation technique. For co-evaporating CIGS2 absorber as a less toxic alternative to Cd-containing film, we analyzed the effect of the CGI-ratio stoichiometry and crystallinity, and explored its opto-electric sensing characteristic of individual solar cell. The results of this research signified the potential of high-performance CIGS2-absorption solar cells for photovoltaic (PV)-module industrial applications. For the optimal CIGS2-absorption film (CGI = 0.95), the Raman main-phase signal (A1) falls at 291 cm-1, which was excited by the 532 nm line of Ar+-laser. Using photo-luminescence (PL) spectroscopy, the corresponding main-peak bandgaps measured was 1.59 eV at the same CGI-ratio film. Meanwhile, the best conversion efficiency (η = 3.212%) and the average external quantum efficiency (EQE = 51.1% in the visible-wavelength region) of photo-electric properties were achieved for the developed CIGS2-solar cells (CGI = 0.95). The discoveries of this CIGS2-absorption PV research provided a new scientific understanding of solar cells. Moreover, this research undeniably contributes to a major advancement towards practical PV-module applications and can help more to build an eco-friendly community.

Spectroscopic analyses of particle and energy aggregations at the interface of silver nanoparticles and fluorescent carbon nanodots.

We study the change in the surface electromagnetic field provided by photoexcited silver nanoparticles as the field is disturbed by fluorescent carbon nanodots. Fluorescent carbon nanodots with an appropriate quantity and quality of surface functional groups are used to mediate the aggregation of silver nanoparticles of matching size and shape to form available nano-size conical structures. Carbon nanodots in the composite absorb and transfer additional photoenergy to the silver surface, resulting in energy aggregation within the cone structure and enhancement of the electromagnetic field in proximity to the silver surface. This elevated energy state is manifested in the strengthening of the SERS signal of the analytical probe 4-aminophenyl disulfide and the mechanism involved is elucidated by additional molecular spectroscopy studies.

Nivolumab-induced acute tubular injury: A case report.

Nivolumab belongs to immune checkpoint inhibitors (ICIs). ICIs-induced kidney injury is rare and acute interstitial nephritis (AIN) is the majority. A 58-year-old woman had gastric cancer treated with nivolumab. Her serum creatinine (Cr) increased to 5.94 mg/dL post 2 cycles of nivolumab and co-administered with acemetacin. A kidney biopsy showed acute tubular injury (ATI). Nivolumab rechallenge was done and Cr worsened again. The lymphocyte transformation test (LTT) indicated a strong positive for nivolumab. Although rare, ATI due to ICIs could not be ruled out, and LTT is a tool to identify the culprit.

Extracellular Matrix-Derived Biophysical Cues Mediate Interstitial Flow-Induced Sprouting Angiogenesis.

Sprouting angiogenesis is orchestrated by an intricate balance of biochemical and mechanical cues in the local tissue microenvironment. Interstitial flow has been established as a potent regulator of angiogenesis. Similarly, extracellular matrix (ECM) physical properties, such as stiffness and microarchitecture, have also emerged as important mediators of angiogenesis. However, the interplay between interstitial flow and ECM physical properties in the initiation and control of angiogenesis is poorly understood. Using a three-dimensional (3D) microfluidic tissue analogue of angiogenic sprouting with defined interstitial flow superimposed over ECM with well-characterized physical properties, we found that the addition of hyaluronan (HA) to collagen-based matrices significantly enhances sprouting induced by interstitial flow compared to responses in collagen-only hydrogels. We confirmed that both the stiffness and matrix pore size of collagen-only hydrogels were increased by the addition of HA. Interestingly, interstitial flow-potentiated sprouting responses in collagen/HA matrices were not affected when functionally blocking the HA receptor CD44. In contrast, enzymatic depletion of HA in collagen/HA matrices with hyaluronidase (HAdase) resulted in decreased stiffness, pore size, and interstitial flow-mediated sprouting to the levels observed in collagen-only matrices. Taken together, these results suggest that HA enhances interstitial flow-mediated angiogenic sprouting through its alterations to collagen ECM stiffness and pore size.

Effectiveness of exercise in improving quality of life in patients with traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. People with TBI exhibit poor quality of life (QOL). Exercise is considered a possible intervention for improving cognitive function and mood, helping improve QOL in patients with TBI. According to our review of the relevant literature, meta-analyses have yet to explore the effect of exercise on QOL in patients with TBI. OBJECTIVES: To determine by meta-analysis of relevant studies whether physical exercise could promote QOL in patients with TBI. METHODS: A systematic review and meta-analysis of intervention studies involving physical exercise for improving QOL outcomes in TBI populations were conducted according to the PRISMA guideline. Our inclusion criteria were as follows: being randomized or nonrandomized controlled trials with quantitative designs that included patients diagnosed with TBI. RESULTS: Thus, six studies met the inclusion criteria. The interventions in four of the six studies had statistically significant effects on QOL improvement. Our meta-analysis revealed a moderate effect size of physical exercise on QOL promotion in patients with TBI. CONCLUSION: For TBI, exercise seems to improve QOL. More research with long-term follow-up should be conducted to assess the effect of exercise on patients with TBI.

Chronic kidney disease and its association with cataracts-A cross-sectional and longitudinal study.

Introduction: We aim to explore the association between chronic kidney disease (CKD) and cataracts. Methods: A total of 121,380 participants with adequate information collected from 29 community-based recruitment centers since 2008 were analyzed. The association between CKD and self-reported diagnosed cataracts was examined in a cross-sectional cohort and was validated in a longitudinal cohort of 25,263 participants without cataracts at baseline. Results and discussion: Of all participants, cataracts occurred in 503/1,947 (26%) and 10,464/119,433 (9%) subjects in the CKD and non-CKD groups, respectively. Multivariate logistic regression showed that CKD was significantly associated with a higher prevalence of self-reported diagnosed cataracts. In the validation cohort, a higher incidence of cataracts was also noted in the CKD group (65/317, 21%) compared to the non-CKD group (1,964/24,252, 8%) during a mean 47-month follow-up. After adjusting for confounders, subjects with CKD had a 1.498-fold higher risk of incident cataracts than those without CKD (95% confidence interval = 1.114 to 2.013, p value = 0.007). We found that CKD was associated with a higher prevalence of cataracts as well as incident cataracts, which suggests CKD patients and their primary physicians should be aware of this disease and can provide a clue for further exploration of the possible mechanisms and treatments.

Habitual Tea Consumption and Risk of Cataracts: A Longitudinal Study.

We aimed to investigate the association between habitual tea consumption and the risk of developing cataracts in a large community-based cohort study. We prospectively collected volunteers from 29 recruitment centers that were ≧ 55 years old with no history of cataracts at the beginning of the study. There were 12,080 participants with available information in our study and were divided into two groups according to habitual tea consumption; non-tea-drinking and tea-drinking groups. The mean age was 59 years. Compared to the non-tea-drinking group, the tea-drinking group had a significantly lower incidence of developing cataracts (15.5% vs 12.1%) during follow-up of 46 months. In multivariate Cox proportional hazards regression analysis, the relative risk (RR) of incident cataracts was lower in the tea-drinking group than the non-tea-drinking group (RR = 0.848; 95% confidence interval [CI] = 0.751 to 0.957). Participants with ≧ 2 cups per day were associated with almost 16% reduction in the risk of developing cataracts compared with the non-tea-drinking group (RR = 0.844; 95% CI = 0.741 to 0.961). Our study suggests that habitual tea consumption can reduce the incidence of cataracts and raises the possibility that the tea content may slow the progression of cataracts.

Fibroblast-derived CXCL12 increases vascular permeability in a 3-D microfluidic model independent of extracellular matrix contractility.

Cancer-associated fibroblasts (CAFs) play an active role in remodeling the local tumor stroma to support tumor initiation, growth, invasion, metastasis, and therapeutic resistance. The CAF-secreted chemokine, CXCL12, has been directly implicated in the tumorigenic progression of carcinomas, including breast cancer. Using a 3-D in vitro microfluidic-based microtissue model, we demonstrate that stromal CXCL12 secreted by CAFs has a potent effect on increasing the vascular permeability of local blood microvessel analogues through paracrine signaling. Moreover, genetic deletion of fibroblast-specific CXCL12 significantly reduced vessel permeability compared to CXCL12 secreting CAFs within the recapitulated tumor microenvironment (TME). We suspected that fibroblast-mediated extracellular matrix (ECM) remodeling and contraction indirectly accounted for this change in vessel permeability. To this end, we investigated the autocrine effects of CXCL12 on fibroblast contractility and determined that antagonistic blocking of CXCL12 did not have a substantial effect on ECM contraction. Our findings indicate that fibroblast-secreted CXCL12 has a significant role in promoting a leakier endothelium hospitable to angiogenesis and tumor cell intravasation; however, autocrine CXCL12 is not the primary upstream trigger of CAF contractility.

Sequential detection of dopamine and L-DOPA by a 2,3-dopa-dioxygenase from Streptomyces sclerotialus.

A variety of enzyme-based colorimetric biosensors have been developed for clinical practice; however, these methods will only become cost-effective when they are able to process multiple samples with a high degree of sensitivity. In this study, a novel heat-stable enzyme, 2,3-dopa-dioxygenase from the thermophilic bacterium Streptomyces sclerotialus (SsDDO), was used in the development of a protein- and cell-based biosensor for the detection of L-DOPA for the first time. SsDDO catalyzes the oxidative cleavage of L-DOPA forms linear semialdehyde (AHMS) and cyclizes to a 3-carboxy-3-hydroxyallylidene-3,4-dihydropyrrole-2-carboxylic acid (CHAPCA). We next derivatized CHAPCA by reacting with 3-aminobenzoic acid (MABA) to yield a red-fluorescent pigment. Overall, the detection of L-DOPA via the red fluorescent signal can be completed in only 30 min. We also developed a sequential analysis method to detect the coexistence of dopamine and L-DOPA with a high degree of sensitivity using the dual-fluorescent signals to monitor the therapy of patients with Parkinson's disease treated with L-DOPA. The robustness and applicability of the system were further validated in serum. In addition, paper microfluidics modified with chitosan was applied for fast and cost-effective analysis of dopamine and L-DOPA in the mixed solutions.

Differential surface partitioning for an ultrasensitive solid-state SERS sensor and its application to food colorant analysis.

Solid-state SERS sensors are desirable point-of-care tools due to their portability. However, the level of SERS sensitivity achieved in liquid phase is rarely duplicated in the solid phase. We report herein the fabrication of a SERS sensor using alumina beads as the solid support and demonstrate its high SERS sensitivity with the model analyte 4-aminophenyl disulfide (4-APDS). The key to sensitivity is a hydrophilic-hydrophobic surface gradient constructed by sequentially coating with the surfactant cetyltrimethylammonium bromide and fluorous 1H,1H,2H,2H-perfluorooctyltriethoxysilane. The surface gradient, together with chloride etching, allows the detection of 4-APDS at the low concentration of 10-15 M. The practicality of the sensor beads is evidenced by successfully tracking the SERS fingerprints of five food colorant standards in the SERS spectra of a popular candy product. These SERS sensor beads are easy to prepare, convenient to use, and highly responsive as a SERS platform for the analysis of colorants.

Rare VPS35 A320V Variant in Taiwanese Parkinson's Disease Indicates Disrupted CI-MPR Sorting and Impaired Mitochondrial Morphology.

Sequence variants in vacuolar protein sorting 35 (VPS35) have been reported to be associated with Parkinson's disease (PD). To investigate if the genetic variants in VPS35 contribute to Taiwanese PD, VPS35 cDNA fragments from 62 patients with PD were sequenced. A cohort of PD (n = 560) and ethnically matched controls (n = 506) were further examined for the identified mutation. The effects of the mutation on cation-independent mannose-6-phosphate receptor (CI-MPR) sorting and mitochondrial morphology were further examined in 293T cells expressing the mutant VPS35. Here, a novel heterozygous A320V in the VPS35 gene was identified in two late-onset PD (LOPD) patients, which was absent in 506 normal controls. Expression of the A320V mutant in 293T cells demonstrated increased colocalization of VPS35 with CI-MPR and decreased CI-MPR and lysosomal-associated membrane protein 2 (LAMP2) levels. Decreased CI-MPR manifested in missorting of cathepsin D and decreased proteolysis of α-synuclein. A320V mutation also increased mitochondrial E3 ubiquitin protein ligase 1 (MUL1) and thus led to mitofusin 2 (MFN2) degradation. The results suggest that the expression of VPS35 A320V leads to disrupted CI-MPR sorting and impaired mitochondrial morphology, which may partly explain its action in PD.

Upper Gastrointestinal Bleeding With Hemobilia Caused by Gallstones.

BACKGROUND: Hemobilia refers to bleeding in the biliary tract, commonly due to iatrogenic, traumatic, and neoplastic causes. It is a rare source of upper gastrointestinal hemorrhage, but it can be severe and fatal. However, gallstones account for 5%-15% of hemobilia cases. CASE REPORT: A 60-year-old woman with diabetes mellitus and chronic kidney disease visited the emergency department with complaints of epigastric pain and vomiting of coffee ground-like content for 2 days. Physical examination revealed epigastric tenderness and hyperactive bowel sounds. Laboratory tests showed anemia with a hemoglobin count of 10.7 mg/dL and elevated liver function tests with total and direct bilirubin levels of 3.6 mg/dL and 2.5 mg/dL, respectively. Panendoscopy showed oozing of coffee ground-like material at the orifice of the ampulla of Vater and second portion of the duodenum, leading to suspicion of hemobilia. After admission, endoscopic retrograde cholangiopancreatography revealed common bile duct (CBD) dilatation with choledocholithiasis, biliary sludge, and filling defect at the middle section of the CBD. Endoscopic sphincterotomy with balloon lithotripsy was performed. After biliary decompression and broad-spectrum antibiotic administration, abdominal pain was relieved, and liver enzyme and total bilirubin levels improved. Symptoms of hemobilia depend on the bleeding rate and presence of bile duct obstructions due to clots. Minor and slow bleeding tend to form clots and cause biliary obstruction. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although minor hemobilia may remain asymptomatic and tends to resolve spontaneously, the cause of hemobilia must be corrected to prevent recurrent bleeding or obstruction.

Ventricular Fibrillation Caused by Primary Carnitine Deficiency.

BACKGROUND: Primary carnitine deficiency (PCD) is a rare but potentially life-threatening genetic disorder if left untreated. Although some patients remain asymptomatic lifelong, a few patients present with hepatic encephalopathy, hypoglycemia, cardiomyopathy, dysrhythmia, and even sudden death. CASE REPORT: A 25-year-old woman with PCD collapsed suddenly while eating lunch. Bystander cardiopulmonary resuscitation (CPR) was performed for 8 min, with automated external defibrillation once before admission. Upon arrival at our emergency department (ED), she was unresponsive without a pulse or spontaneous breathing. The initial heart rhythm on the electrocardiogram monitor was ventricular fibrillation (VF). The medical staff continued CPR with defibrillation for sustained VF. Return of spontaneous circulation (ROSC) was achieved after a total resuscitation time of 14 min, with defibrillation twice after cardiac arrest. The heart rhythm after ROSC was atrial fibrillation, with a rapid ventricular rate initially and subsequent progression to sinus tachycardia with diffuse ST segment depression and a prolonged QT interval. Her low carnitine level was consistent with her underlying disease. Cardiac magnetic resonance imaging and sonography for detection of cardiomyopathy showed no significant findings. With carnitine supplementation for a few days, her plasma carnitine level returned to 30 µM, with no recurrence of ventricular dysrhythmia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: PCD is rare but could be life-threatening, and compiling detailed histories may help emergency physicians to determine the cause of sudden cardiac death after resuscitation. This information may be used to correct potential underlying problems and prevent recurrence of the condition after treatment.

Distinguishing Specific CXCL12 Isoforms on Their Angiogenesis and Vascular Permeability Promoting Properties.

Angiogenesis is associated with increased vessel sprouting and permeability. Important mediators of these angiogenic responses include local environment of signaling molecules and supporting extracellular matrix (ECM). However, dissecting the interplay of these instructive signals in vivo with multiple cells and extracellular molecules remains a central challenge. Here, microfluidic biomimicry is integrated with 3D ECM hydrogels that are well-characterized for molecular-binding and mechanical properties to reconstitute vessel-like analogues in vitro. This study focuses on three distinct isoforms of the pro-metastatic chemokine CXCL12. In collagen-only hydrogel, CXCL12-α is the most potent isoform in promoting sprouting and permeability, followed by CXCL12-ß and CXCL12-γ. Strikingly, addition of hyaluronan (HA), a large and negatively charged glycosaminoglycan, with collagen matrices selectively increases vessel sprouting and permeability conferred by CXCL12-γ. This outcome is supported by the measured binding affinities to collagen/HA ECM, suggesting that negatively charged HA increases the binding of CXCL12-γ to augment its angiogenic potency. Moreover, it is shown that addition of HA to collagen matrices on its own decreases vessel sprouting and permeability, and these responses are nullified by blocking the HA receptor CD44. Collectively, these results demonstrate that differences in binding to extracellular HA help underlie CXCL12 isoform-specific responses toward directing angiogenesis.

Physical organic studies and dynamic covalent chemistry of picolyl heterocyclic amino aminals.

A dynamic covalent system of the picolyl heterocyclic amino aminals has been studied. The aminals are characterized as a metastable species and easily switch to other forms via external stimuli. The solvent, temperature, acid-base and substituent effects have been examined to evaluate the dynamic covalent system. The results reveal that a more polar solvent, a lower temperature, basic conditions and an electron-withdrawing moiety contribute to the stabilities of aminals. The existence of the n → π* interaction between acetonitrile and the C[double bond, length as m-dash]N moiety makes the N-pyrimidyl imine (4c and 4d) yield higher in CD3CN. In a similar fashion, all aminals tend to convert to the corresponding hemiaminal ethers in a methanol environment. According to these findings, we successfully synthesized the following species: (a) N-2-picolylpyrimidin-2-amine 6c obtained by reduction using acetonitrile as the specific solvent; (b) a picolyl aromatic amino aminal 3e prepared from 2-pyridinecarboxaldehyde and the electron withdrawing 2-methoxy-5-nitroaniline.

CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan.

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by clustered enlarged capillary-like channels in the central nervous system. The genes harboring variants in patients with CCM include CCM1/Krev interaction trapped-1, CCM2/MGC4607, and CCM3/programmed cell death protein 10. We aimed to identify pathogenic variants in an ethnic Chinese population in Taiwan. We recruited 95 patients with multiple CCMs or a single lesion with a relevant family history. Sanger sequencing was performed for 41 patients. Variants were identified using sequence alignment tools, and the clinical significance of these variants was determined using American College of Medical Genetics and Genomics standards and guidelines. Several pathogenic variants were found in six patients, including three unrelated patients and three affected members of one family. Two novel pathogenic variants leading to early truncation comprised a deletion variant in exon 18 of CCM1 (c.1846delA; p.Glu617LysfsTer44) and an insertion variant in exon 4 of CCM2 (c.401_402insGCCC; p.Ile136AlafsTer4). One novel pathogenic splice site variant was c.485 + 1G > C at the beginning of intron 8 of CCM1. In this study, we identified novel variants related to CCM in an ethnically Chinese population in Taiwan.

Application of microscale culture technologies for studying lymphatic vessel biology.

Immense progress in microscale engineering technologies has significantly expanded the capabilities of in vitro cell culture systems for reconstituting physiological microenvironments that are mediated by biomolecular gradients, fluid transport, and mechanical forces. Here, we examine the innovative approaches based on microfabricated vessels for studying lymphatic biology. To help understand the necessary design requirements for microfluidic models, we first summarize lymphatic vessel structure and function. Next, we provide an overview of the molecular and biomechanical mediators of lymphatic vessel function. Then we discuss the past achievements and new opportunities for microfluidic culture models to a broad range of applications pertaining to lymphatic vessel physiology. We emphasize the unique attributes of microfluidic systems that enable the recapitulation of multiple physicochemical cues in vitro for studying lymphatic pathophysiology. Current challenges and future outlooks of microscale technology for studying lymphatics are also discussed. Collectively, we make the assertion that further progress in the development of microscale models will continue to enrich our mechanistic understanding of lymphatic biology and physiology to help realize the promise of the lymphatic vasculature as a therapeutic target for a broad spectrum of diseases.

Plasma and Serum Alpha-Synuclein as a Biomarker of Diagnosis in Patients With Parkinson's Disease.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and α-synuclein plays a critical role in the pathogenesis of PD. Studies have revealed controversial results regarding the correlation between motor severity and α-synuclein levels in peripheral blood from patients with PD. Objective: We examined α-synuclein levels in plasma or serum in patients with PD and investigated the relationship between plasma or serum α-synuclein level and motor symptom severity. Methods: We recruited 88 participants (48 patients with PD and 40 healthy controls). Clinical information was collected, and venous blood was drawn from each participant to be processed to obtain plasma or serum. The plasma or serum α-synuclein level was detected using monoclonal antibodies with magnetic nanoparticles, and was measured through immunomagnetic reduction. Plasma or serum α-synuclein levels were quantitatively detected. Results: In patients with PD, the means of plasma and serum α-synuclein level were 3.60 ± 2.53 and 0.03 ± 0.04 pg/mL, respectively. The areas under the receiver operating characteristic curve of plasma and serum α-synuclein for distinguishing patients with PD from healthy controls were 0.992 and 0.917, respectively. The serum α-synuclein level also showed a significant correlation with patients in H-Y stages 1-3 (r = 0.40, p = 0.025), implying that the serum α-synuclein level may be a potential marker of motor symptom severity in patients with early PD. Conclusions: Our data suggest that the α-synuclein level in serum or plasma can differentiate between healthy controls and patients with PD. Serum α-synuclein levels moderately correlate with motor severity in patients with early PD.

Genetic and functional characters of GRN p.T487I mutation in Taiwanese patients with atypical parkinsonian disorders.

BACKGROUND: Mutations in the GRN (granulin precursor) are a frequent cause of frontotemporal dementia (FTD) and other atypical parkinsonian disorders. However, the frequency of GRN mutations in Asian patients with atypical parkinsonian disorders is still uncertain. METHODS: We screened GRN mutations by sequencing cDNA from 98 patients with FTD or atypical parkinsonian disorders. The functional properties of the identified mutation were evaluated by overexpression in human embryonic kidney (HEK)-293 cells. RESULTS: We identified a new missense (GRN p.T487I) mutation in a female patient with undefined atypical parkinsonism. The overexpression experiment further demonstrated that p.T487I mutation reduced the progranulin protein level and stability in HEK-293 cells. CONCLUSION: GRN p.T487I mutation, which decreases the stability of progranulin protein, could be a new causative mutation in patients with atypical parkinsonian disorders.